Figure 1. Structure of adenovirus (Viral zone website)

Adenovirus (AdV) is a non-enveloped, double-stranded DNA virus with a diameter of approximately 70-90 nm (Figure 1). Its genome is about 36 kb in size and is divided into early (E1A, E1B, E2, E3, E4), intermediate (IVa2, pIX), and late (L1-L5) transcription units (Figure 2). There are over 50 serotypes of AdV, with Ad5 being the most commonly used. AdVs exhibit tissue tropism and the ability to infect both dividing and non-dividing cells. Commonly used AdV vectors are categorized into conditionally replicating adenoviruses (CRAs; oAds) and replication-deficient adenoviruses. These vectors are widely used in the development of preventive vaccines, therapeutic vaccines, and oncolytic viruses.

Figure 2. Genome structure of adenovirus (A Handbook of Gene and Cell Therapy)

Conditionally replicating AdV vectors can specifically replicate in cancer cells by mutating or altering the expression of the E1 gene. AdV E1A CR2 or E1B55K interfere with the host cell cycle through the retinoblastoma protein (Rb) and p53 signaling pathways, forcing normal cells into the S phase for replication. When E1A CR2 or E1B55K is deleted, cell division is inhibited, preventing viral replication in normal cells but allowing for extensive replication in cancer cells with abnormal Rb and p53 regulation.

Oncolytic adenoviruses (oAds) are engineered viruses based on AdV that can specifically kill tumor cells. They are widely studied and applied due to their broad host range, safety, ease of production, and capacity to carry large exogenous genes.